rs17724172

Positions:

• chr18-3512218-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004746.4(DLGAP1):​c.2480-3557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,146 control chromosomes in the GnomAD database, including 2,274 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2274 hom., cov: 32)
• Consequence: DLGAP1 NM_004746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4	c.2480-3557A>G		intron_variant		ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8	c.2480-3557A>G		intron_variant		5	NM_004746.4	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25190 AN: 152028 Hom.: 2277 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25186 AN: 152146 Hom.: 2274 Cov.: 32 AF XY: 0.169 AC XY: 12575 AN XY: 74392

Gnomad4 AFR AF: 0.0992

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.192

Alfa AF: 0.194 Hom.: 4063

Bravo AF: 0.160

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.3
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17724172; hg19: chr18-3512216;